THE ROLE OF SMALL-INTESTINAL ANTIGEN-PRESENTING CELLS IN THE INDUCTION OF T-CELL REACTIVITY TO SOLUBLE-PROTEIN ANTIGENS - ASSOCIATION BETWEEN ABERRANT PRESENTATION IN THE LAMINA PROPRIA AND ORAL TOLERANCE

The oral administration of soluble protein antigen results in profound immunological tolerance. However, the tissue location and function of antigen-presenting cells (APC) that stimulate this response remain un clear. We have hypothesized that the properties of cells presenting an tigen to naive T cells within the gut are involved, and therefore gut APC should stimulate T-cell responses with different characteristics t o those induced by other APC. To test this, we studied in vitro primar y T-cell responses following presentation of soluble protein antigen b y cells from the Peyer's patches (PPC) and lamina propria (LPC) of the murine small intestine and the spleen (SPLC). Each APC population sti mulated antigen-specific proliferative responses with similar anamnest ic characteristics; however, analysis of the cytokines produced reveal ed marked differences. Whereas SPLC stimulated the balanced production of T-helper type 1 (Th1) and Th2 cytokines, PPC induced a profile con sistent with the provision of T-cell help for IgA production. Interest ingly, presentation of antigen by LPC stimulated high levels of interf eron-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) in the absence of other cytokines [interleukin-2 (IL-2), IL-4, IL-5]. Evidence from analysis of cell activation and division within the cult ures suggested that this profile may result from the preferential acti vation of CD8(+) T cells by LPC; however, the lack of conventional CD4 (+) T-cell cytokines indicated a defect in the normal function of thes e cells. Adoptive transfer of antigen-pulsed LPC to syngeneic animals abrogated the induction of delayed-type hypersensitivity (DTH) respons iveness, which followed a subsequent conventional antigen challenge fu rther suggesting a role for lamina propria APC in tolerance induction.